Sweatman: Rx of Renal Cancer Flashcards
these questions are probably more detailed than need be. Also the toxicities of drugs don't include myelosuppression bc thats a no-brainer
What is the best curative treatment in renal cancer?
surgical excision
What are common sites of metastatic growth in renal tumors?
lymph nodes (most common) lung, liver, bone (destructive lesions) adrenal gland brain opposite kidney subcutaneous skin nodules
What is the most common renal tumor in children called?
Nephroblastoma (Wilm’s Tumor)
T or F: WIlm’s tumor is highly curable
T. 5 year survival rate is consistently above 90%
Standard chemotherapy postnephrectomy in pts with Wilm’s tumor involves 3 different regimen options. Each one has what drug in common?
Vincristine
- Vincristine + dactinomycin (18 weeks)
- Vincristine + dactinomycin + doxorubicin (24 weeks)
- Vincristine + doxorubicin +cyclophosphamide + etopside (24 weeks)
Treatment for recurrent disease in Wilm’s tumor patients involves alternating courses of what two tx regimens?
- Vincristine, doxorubicin, cyclophosphamide
2. etopside and cyclophosphamide
T or F: treatment of clear cell sarcoma is similar to the treatment of nephroblastoma (wilm’s tumor)
T. treatment options involves 2 standard regimens used in the treatment of Wilm’s tumor PLUS RADIATION THERAPY
Patients with recurrent clear cell sarcoma involving the brain have benefited from what tx?
ICE (ifosfamide, carboplatin, etopside) coupled with local control (surgical resection and/or radiation)
In the tx of childhood tumors, all of the drugs have a similar ROA…?
IV
Carboplatin toxicities
infection susceptibility
cyclophosphamide and ifosfamide toxicities
hemorrhagic cystitis
what can you use to treat the toxicity of cyclophosphamide and ifosfamide?
MESNA to treat hemorrhagic cystitis
doxorubicin toxicities
acute and chronic cardiotoxicity
dactinomycin toxicities
hepatic dysfunction
infection susceptibility
etopside toxicities
hematologic toxicity
BP instability
vincristine toxicities
bilateral sensory “stocking-glove” pattern
What are examples of rapamycins?
temsirolimus
everolimus
What is the MOA of rapamycins? net effects?
bind to FKBP12 and inhibit mTORC1
this inhibits cell cycle progression and angiogenesis and promotes apoptosis
In terms of ROA and dosing regimen, how do temsirolimus and everolimus differ?
temsirolimus: IV weekly
everolimus: oral daily
What metabolizes both temsirolimus and everolimus? how is temsirolimus somewhat different?
CYP3A4
temsirolimus is metabolized to sirolimus, likely a more important agent
What are prominent side effects of temsirolimus and everolimus?
maculopapular rash
mucositis
anemia
fatigue
What are less frequent side effect of temsirolimus and everolimus seen with progressive drug cycles?
reversible leukopenia
thrombocytopenia
How can temsirolimus and everolimus affect the pulmonary system? Tx for this?
pulmonary infiltrates
can lead to cough, SOB
stop drug (duh) prednisone
What are the TKIs used in the tx of adult renal tumors?
sunitinib
sorafenib
pazopanib
What do all 3 TKIs inhibit?
VEGF-receptor 2 and other tyrosine kinases
there is a long list of other tyr kinases for each drug. you should probably look at them.
ROA for the 3 TKIs? Metabolism?
oral
CYP3A4
Response to which TKI is better (31%) and longer lasting than for other antiangiogenic drugs?
sunitinib
What are common vascular toxicities observed with antiangiogenic drugs (i.e. TKIs)?
bleeding
HTN
arterial thrombotic events
What are specific side effects of sunitinib?
fatigue
hypothyroidism
CHF (often with HTN)
hand foot syndrome
What is the BBW for pazopanib? What does this call for?
hepatic disease: severe and fatal hepatotoxicity has been reported
liver function tests before tx, at least once weekly during first 4 months of tx, and periodically after
What are some other side effects of pazopanib?
hyperbilirubinemia, especially in Gilbert’s syndrome which involves glucuronidation deficiency and reduced excretion of bilirubin)??
T or F: interferon-alpha alone is more effective in tx of metastatic renal cell carcinoma when compared to inf-alpha + bevacizumab
F. adding bevacizumab to interferon alfa results in significant imporvement in progression-free survival, when comapred to inf-alfa alone
what is the MOA of bevacizumab?
VEGF inhibitor
What are the main safety concerns associated with bevacizumab?
HTN arterial thromboembolic events (stroke, angina, MI) wound healing complications GI perforations proteinuria
What is aldesleukin?
recombinant IL-2
Aldesleukin was designated as a ____ drug for renal cell carcinoma
orphan
(an orphan drug is one that was developed specifically to tx a rare condition. often pharmaceutical companies are given incentives to develop orphan drugs)
What is the MOA of aldesleukin?
- binds IL-2 receptor on cells of the immune system
- stimulates a cytokine cascade
- may stimulate cytotoxic lymphocytes
How does T sweat describe aldesleukin?
“VERY nasty stuff!”
There are over 120 adverse events listed for aldesleukin. Name them all. actually, just name the 2 T sweat listed.
- capillary leak syndrome–>loss of vascular tone (THIS IS RESPONSIBLE FOR MANY OF THE ADVERSE EFFECTS)
- decreased mean arterial pression (MAP)–>decreased organ perfusion
What is the MOA of interferon-alpha?
direct antiproliferative effect on the tumor cell by
- enhance or inhibit protein synthesis
- modify cell surface antigen expression
- modulate immune system
What are the net effects of interferon-alpha?
immunomodulatory effects: it induces a host response to the tumor which slows the rate of cell proliferation
What are some side effects of interferon alpha?
neuropsychiatric: suicide homicidal and suicidal ideation depression relapse of drug addiction aggressive behavior
T or F: interferon alfa provides a modest survival benefit compared to other commonly used treatments and should be considered for the control arm of future studies of systemic agents
Fact (so, true, not false)
